Genetic analysis of a congenital nephrogenic diabetes insipidus pedigree

Abstract

Background As an X-linked recessive way, arginine vasopressin receptor 2 (AVPR2) gene mutation resulted in a hereditary disease — congenital nephrogenic diabetes insipidus (CNDI). We found a suspect clinical CNDI pedigree. In order to identify the genetic etiology, we performed the genetic analysis. Methods The clinical features of the proband and his family members were recorded. The laboratory tests and imaging inspections were analyzed. The water deprivation and pituitrin loading test were performed in the proband and his brother. The genomic DNA of all the members of the pedigree was extracted and then PCR amplification on AVPR2 gene was carried out. Sequencing in both directions was performed to identify mutation on AVPR2 gene. Results Both the proband and his brother were diagnosed as CNDI, meanwhile the other members of this pedigree were normal. No severe biochemical abnormality was found in the two CNDI patients. Both the patients had moderate urinary retention, severe megaloureter and hydronephrosis, and mild renal insufficiency. Two mutations of AVPR2 gene were discovered in the 3rd exon in the patients, a silent mutation L309L and a nonsense mutation R337X. The AVPR2 gene R337X mutation was co-segregated with CNDI. R337X mutation was not a reported mutation in the mainland of China. Conclusion The AVPR2 gene R337X mutation was also a genetic etiology of CNDI patients in the mainland of China.